WIRINGHUMANCOGNITION Report Summary

Executive summaryThis project addressed a fundamental question: what makes us human? We approached this far-reaching question from a neuroscientific and evolutionary perspective: the project was tailored to compare the anatomy of our human brains to those of our ape and monkey relatives. Specifically, we focussed on the white matter connections linking temporal and frontal regions of the brain. This neural architecture underpins vital aspects of our human nature, including our emotional, social, and language skills. Perturbations of this system are implicated in psychiatric disorders, such as depression and aggression. In light of the wide range of behavioural abilities of monkeys, apes, and humans we found remarkable consistency in the organisational principals of the neuroanatomy. For example, in all primates, we mapped a commonly ignored pathway, linking the amygdala to the prefrontal cortex, in unprecedented detail. We showed how it differed from other tracts running close by, such as the uncinate fascicle and the internal capsule. The anatomy of this pathway suggests it is involved in emotion, reward, and decision making, and could be targeted by deep-brain stimulation to treat affective disorders. On top of these connectional principals shared across primates we observed species-specific adaptations. For example, human uncinate fascicle and extreme capsule fibres projected more strongly to lateral prefrontal cortex than in the monkey brain. Also, while the core of two main tracts in the temporal lobe, the middle and inferior longitudinal fascicles, showed strong similarities across the human, monkey, and ape brain, we observed evidence that peripheral branching of the human middle longitudinal fascicle was extended. In summary, our findings suggest that the human brain is in fact not dramatically different from our primate relatives, but rather that the sum of many smaller adaptations together enables uniquely human cognition.

Description of project context and objectivesOur human cognitive skills eclipse those of our primate relatives in many domains, ranging from logical reasoning to managing complex social lives, and from tool-use to language. The difference in behaviour is striking, yet our brains seem to be organised along very similar principles. This project aims to simultaneously identify those fundamental principles while highlighting where variations on those principles can have major consequences for species unique abilities. We focus our research on one characteristically human ability and the brain architecture that is proposed to underlie it. Compared to other primates, humans can learn the abstract structure of their surroundings exceptionally quickly, almost instantly inferring the relations that bind individual objects and events. This faculty likely relies on the interactions between the temporal and prefrontal cortex, two regions that have underwent dramatic expansion in human evolution. Instead of studying these regions in isolation, here we focus on the white matter fibres connecting them, following the notion that the function of a system as a whole is strongly shaped by the interactions of its computational nodes. Future projects resulting from the current work will focus on the functions that those connections support.

Description of the main S&T results/foregroundsThe scientific fields of neuroscience and evolutionary biology rely heavily on the macaque monkey as an animal model for the human brain. However, the macaque monkey is not a close relative to the human – our common ancestor having lived about 25 million years ago – and the neuroanatomy of the different species are conventionally studied using different techniques. This project aimed to bridge these two divides simultaneously by acquiring and analysing magnetic resonance imaging (MRI) data from post-mortem macaque monkeys, a gorilla ape, and in-vivo humans. MRI provides the opportunity to image the brain in its entirety and non-invasively. Different MRI protocols allow for mapping of different structural features and functional haemodynamics. Most relevant for the current project, diffusion MRI (dMRI) allows one map white matter connections in the brain. Below we will highlight some of the results of the project, for a comprehensive overview we refer to the work published in open-access journals.

First, we improved existing tools and developed new processing pipelines by analysing a post-mortem macaque sample that had been acquired earlier (to estimate the project’s feasibility). These advances included improvements to spatial distortion correction, RF bias-field correction, susceptibility artefact correction, T1-weighted and T2-weighted contrast inversion, and automated brain extraction. After establishing the success of these analytical advances, we acquired diffusion and structural MRI of three new post-mortem macaque monkeys and one gorilla ape. We focussed our analyses primarily on the connections between the temporal and frontal lobes, most specifically on the prefrontal projections of the amygdala. We mapped this connectional system in unprecedented detail, uncovering previously unknown organisational principles.

We observed that the main fibres projecting from the amygdala to the prefrontal cortex ran a different course than what was previously considered textbook knowledge in the field. We identified these as the amygdalofugal pathway, running segregated from the uncinate fascicle, the internal, external, and extreme capsules and cingulum bundle. While this pathway eventually joins the uncinate it only does so after reaching subcortical structures that play a central role in decision making, motivation, and control. As such this pathway seems to directly link up evolutionary “old” subcortical regions, with “novel” cortical grey matter regions.

On top of these organisational principles that were shared across all studied primates we observed species-unique variations. For example, we found that temporal-prefrontal projections in the human, compared to the macaque, were extended specifically to lateral prefrontal cortex, while human subcortical-prefrontal projections were extended to the frontal pole. Using a data-driven parcellation approach we found the main fibre bundle running along the lateral temporal cortex (middle longitudinal fascicle) to exhibit additional branching in the human compared to gorilla and macaque brain. In contrast, the “skeleton” of the white matter bundles in the temporal lobe was highly preserved across species.

The results obtained from post-mortem primate MRI could be directly compared to in-vivo macaque and human data, allowing us to take translational steps already as part of the current project. We analysed a unique dMRI dataset of 20 macaques whose social hierarchy has been carefully mapped. Using tools developed in the context of this project we will analyse the integrity and projections of white matter bundles as a factor of social group size and position in the hierarchy. This would allow us to identify connectional systems that underpin social cognition in primates. In parallel, we have employed our analysis tools to study the organisational principles of the human brain using a very large cohort of 900 subjects, made publically available in the context of the Human Connectome Project. Preliminary results suggest that the temporal lobe is characterised by a patchy organisation with gradual changes in connectivity, contrasting to the rather more step-wise changing connectional patterns present in other brain lobes.

The potential impact (socio-economic, societal, dissemination activities, exploitation)This project addressed a question that carries an intrinsic interest of the general public and is of great relevance to our society: what makes us human? Moreover, the detailed anatomical insights achieved in the project will inform functional studies of human cognition. In addition, these insights can also help to target clinical interventions. The systems we studied, especially the connections between subcortical and prefrontal regions, are principally involved in psychiatric and affective disorders, such as obsessive compulsive disorder and depression. Current treatment options are often anatomically – and consequentially cognitively – a-specific, consider for example the wide-spread effects of serotonin re-uptake inhibitors. Surprisingly, even anatomically targeted options, such as last-resort deep-brain stimulation, are currently targeted at regions much larger than the fine organisation the current work has revealed. The analytical advances emerging from this project have already been made available to the public as part of an open-source software toolbox. All results will be published with open-access for the public, and we plan to make brain atlases arising from future work similarly available. Most of the results of the project have been communicated to the scientific and general public during conferences, lectures, and public symposia. We hope that the work resulting from this project will lead to new insights in human neuroanatomy, cognition, and evolution, while providing fundamental advances to translate these insights to the clinic.